Bernard‐Soulier syndrome in Pakistan: Biochemical and molecular analyses leading to identification of a novel mutation in <i><scp>GP</scp>1<scp>BA</scp></i>

Boeckelmann, Doris; Naz, Arshi; Siddiqi, Muhammad Younus Jamal; Lerner, E A; Sandrock-Lang, Kirstin; Shamsi, Tahir; Zieger, Barbara

doi:10.1111/hae.13365

Cited by 3 publications

(3 citation statements)

References 13 publications

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“…In our patients consanguinity was common. The common occurrence of marriage among cousins may lead to a higher occurrence of this disease in our country 19…”

Section: Discussionmentioning

confidence: 93%

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Bernard Soulier Syndrome: 10 years’ experience at a tertiary care hospital

Farhan¹,

Iqbal

Ahmed³

2019

Pak J Med Sci

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Objective: To determine clinical manifestations and laboratory findings in patients with BSS diagnosed through platelet aggregometry followed in a tertiary care hospital in Lahore, Pakistan. Methods: The retrospective study comprised patients who presented in Hematology and Transfusion Medicine Department of The Children Hospital & Institute of Child Health, Lahore with the relevant diagnosis from 2006 to 2013. The result of all the patients were collected on a predesigned proforma. Medical data was scrutinized to collect age, gender, clinical findings along with results of complete blood count, bleeding time and platelet aggregation studies for the diagnosis of Bernard Soulier Syndrome. Results: Among 49 patients, 26 patients were females and 23 males. The mean age of the patients was 5±2.5 years. 81% had a family history of consanguinity. The most common presenting symptom included epistaxis seen in 73.4% patients. Complete blood count demonstrated decreased platelets in 85.7% of patients ranging from 20 X 109/L to 130 X 109/L. Anemia was seen in 67.3% and 93.8% had prolonged bleeding time. Peripheral blood smears demonstrated giant platelets in all patients. The majority of patients 65.3% had mild bleeding episodes. Platelet aggregation studies showed normal aggregation with ADP, Collagen and Epinephrine in 100% of our patients whereas all showed no response of aggregation with Ristocetin. Conclusion: Our data is consistent with other reports regarding clinical presentation of BSS, but we report large number of BSS patients from our area, emphasizing significance to provide diagnostic services in Pakistan to find out exact magnitude of disease. doi: https://doi.org/10.12669/pjms.35.3.980 How to cite this:Farhan S, Iqbal I, Ahmed N. Bernard Soulier Syndrome: 10 years’ experience at a tertiary care hospital. Pak J Med Sci. 2019;35(3):---------. doi: https://doi.org/10.12669/pjms.35.3.980 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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“…In our patients consanguinity was common. The common occurrence of marriage among cousins may lead to a higher occurrence of this disease in our country 19…”

Section: Discussionmentioning

confidence: 93%

“…BSS like all autosomal recessive disorders is common in communities where incidence of consanguineous marriages is high emphasizing the need of identification of genetic mutations. From Pakistan, only a single report regarding genetic mutations in BSS patients is available 19…”

Section: Discussionmentioning

confidence: 99%

Bernard Soulier Syndrome: 10 years’ experience at a tertiary care hospital

Farhan¹,

Iqbal

Ahmed³

2019

Pak J Med Sci

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“…11 Other pathogenic variants in GP9 are frequent in the Japanese population (p.Cys89Tyr or p.Trp143*) 10 12 or in patients from India or Pakistan (p.Cys24Arg). 13 14 15 BSS is inherited as either autosomal recessive or (more rarely) autosomal dominant. 16 Monoallelic pathogenic variants in GP1BA and GP1BB are responsible for the autosomal dominant trait.…”

Section: Introductionmentioning

confidence: 99%

Pathogenic Aspects of Inherited Platelet Disorders

et al. 2021

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Inherited platelet disorders (IPDs) constitute a large heterogeneous group of rare bleeding disorders. These are classified into: (1) quantitative defects, (2) qualitative disorders, or (3) altered platelet production rate disorders or increased platelet turnover. Classically, IPD diagnostic is based on clinical phenotype characterization, comprehensive laboratory analyses (platelet function analysis), and, in former times, candidate gene sequencing. Today, molecular genetic analysis is performed using next-generation sequencing, mostly by targeting enrichment of a gene panel or by whole-exome sequencing. Still, the biochemical and molecular genetic characterization of patients with congenital thrombocytopathias/thrombocytopenia is essential, since postoperative or posttraumatic bleeding often occurs due to undiagnosed platelet defects. Depending upon the kind of surgery or trauma, this bleeding may be life-threatening, e.g., after tonsillectomy or in brain surgery. Undiagnosed platelet defects may lead to additional surgery, hysterectomy, pulmonary bleeding, and even resuscitation. In addition, these increased bleeding symptoms can lead to wound healing problems. Only specialized laboratories can perform the special platelet function analyses (aggregometry, flow cytometry, or immunofluorescent microscopy of the platelets); therefore, many IPDs are still undetected.

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Glanzmann Thrombasthenia in Pakistani Patients: Identification of 7 Novel Pathogenic Variants in the Fibrinogen Receptor αIIbβ3

Siddiqi

Boeckelmann

Naz

et al. 2023

Cells

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Glanzmann thrombasthenia (GT) is a rare autosomal recessive inherited platelet disorder occurring frequently in populations with high incidence of consanguineous marriages. GT is characterized by quantitative and/or qualitative defect of the platelet αIIbβ3 (GPIIb/IIIa) receptor caused by pathogenic variants of the encoding genes: ITGA2B and ITGB3. Patients present with a moderate to severe bleeding tendency with normal platelet count. Platelets show reduced/absent aggregation for all agonists except ristocetin in light transmission aggregometry and reduced/absent αIIbβ3 expression in flow cytometry (FC). In this study, we investigated a cohort of 20 Pakistani patients and 2 families collected from the National Institute of Blood Disease, Karachi and Chughtai’s Lab, Lahore. Platelet aggregation studies, FC (platelet CD41, CD61, CD42a, CD42b) and direct sequencing of the candidate genes were performed. All patients showed altered platelet aggregation, but normal agglutination after stimulation with ristocetin. Absent/reduced αIIbβ3 receptor expression was present in the platelets of 16 patients, in 4 patients expression was borderline/normal. Candidate gene sequencing identified pathogenic/likely pathogenic variants in 15 patients. Seven variants are novel. One patient with absent receptor expression remained without genetic finding. 13 (86.7%) of 15 patients stated consanguinity reflected by homozygosity finding in 14 (93.3%) patients.

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Bernard‐Soulier syndrome in Pakistan: Biochemical and molecular analyses leading to identification of a novel mutation in GP1BA

Cited by 3 publications

References 13 publications

Bernard Soulier Syndrome: 10 years’ experience at a tertiary care hospital

Bernard Soulier Syndrome: 10 years’ experience at a tertiary care hospital

Pathogenic Aspects of Inherited Platelet Disorders

Glanzmann Thrombasthenia in Pakistani Patients: Identification of 7 Novel Pathogenic Variants in the Fibrinogen Receptor αIIbβ3

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